Dataset Information

Possible Contribution of Alternative Transcript Isoforms in Mature Biofilm Growth Phase of Candida glabrata.

ABSTRACT: Expression of genome-wide alternative transcript isoforms and differential transcript isoform usage in different biological conditions (isoform switching) are responsible for the varied proteomic functional diversity in higher eukaryotic organisms. However, these mechanisms have not been studied in Candida glabrata, which is a potent eukaryotic opportunistic pathogen. Biofilm formation is an important virulence factor of C. glabrata that withstands antifungal drug stress and overcomes the host-immune response. Here, we present the genome-wide differential transcript isoform expression (DTE) and differential transcript isoform usage (DTU) in a mature biofilm growth phase of C. glabrata (clinical isolate; NCCPF 100,037) using the RNA sequencing approach. The DTE analysis generated 7837 transcript isoforms from the C. glabrata genome (5293 genes in total), and revealed that transcript isoforms generated from 292 genes showed significant DTU in the mature biofilm cells. Gene ontology, pathway analysis and protein-protein interactions of significant transcript isoforms, further substantiated that their specific expression and differential usage is required for transitioning the planktonic cells to biofilm in C. glabrata. The present study reported the possible role of expression of alternative transcript isoforms and differential transcript isoform usage in the mature biofilms of C. glabrata. The observation derived from the study may prove to be beneficial for making future antifungal therapeutic strategies.

Supplementary information

The online version contains supplementary material available at 10.1007/s12088-022-01036-7.

SUBMITTER: Raj K

PROVIDER: S-EPMC9705674 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Possible Contribution of Alternative Transcript Isoforms in Mature Biofilm Growth Phase of Candida glabrata.

Raj Khem K Rishi Praveen P Shukla Geeta G Rudramurhty Shivaprakash M SM Mongad Dattatray S DS Kaur Amrita A

Indian journal of microbiology 20220827 4

Expression of genome-wide alternative transcript isoforms and differential transcript isoform usage in different biological conditions (isoform switching) are responsible for the varied proteomic functional diversity in higher eukaryotic organisms. However, these mechanisms have not been studied in Candida glabrata, which is a potent eukaryotic opportunistic pathogen. Biofilm formation is an important virulence factor of C. glabrata that withstands antifungal drug stress and ...[more]

PMID: 36458226

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Project description:Candida is a member of the normal human microbiota and often resides on mucosal surfaces such as the oral cavity or the gastrointestinal tract. In addition to their commensality, Candida species can opportunistically become pathogenic if the host microbiota is disrupted or if the host immune system becomes compromised. An important factor for Candida pathogenesis is its ability to form biofilm communities. The two most medically important species-Candida albicans and Candida glabrata-are often coisolated from infection sites, suggesting the importance of Candida coculture biofilms. In this work, we report that biofilm formation of the coculture population depends on the relative ratio of starting cell concentrations of C. albicans and C. glabrata When using a starting ratio of C. albicans to C. glabrata of 1:3, ∼6.5- and ∼2.5-fold increases in biofilm biomass were observed relative to those of a C. albicans monoculture and a C. albicans/C. glabrata ratio of 1:1, respectively. Confocal microscopy analysis revealed the heterogeneity and complex structures composed of long C. albicans hyphae and C. glabrata cell clusters in the coculture biofilms, and reverse transcription-quantitative PCR (qRT-PCR) studies showed increases in the relative expression of the HWP1 and ALS3 adhesion genes in the C. albicans/C. glabrata 1:3 biofilm compared to that in the C. albicans monoculture biofilm. Additionally, only the 1:3 C. albicans/C. glabrata biofilm demonstrated an increased resistance to the antifungal drug caspofungin. Overall, the results suggest that interspecific interactions between these two fungal pathogens increase biofilm formation and virulence-related gene expression in a coculture composition-dependent manner.IMPORTANCECandida albicans and Candida glabrata are often coisolated during infection, and the occurrence of coisolation increases with increasing inflammation, suggesting possible synergistic interactions between the two Candida species in pathogenesis. During the course of an infection, the prevalence of each Candida species may change over time due to differences in metabolism and in the resistance of each species to antifungal therapies. Therefore, it is necessary to understand the dynamics between C. albicans and C. glabrata in coculture to develop better therapeutic strategies against Candida infections. Existing in vitro work has focused on understanding how an equal-part culture of C. albicans and C. glabrata impacts biofilm formation and pathogenesis. What is not understood, and what is investigated in this work, is how the composition of Candida species in coculture impacts overall biofilm formation, virulence gene expression, and the therapeutic treatment of biofilms.

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Possible Contribution of Alternative Transcript Isoforms in Mature Biofilm Growth Phase of Candida glabrata.

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Possible Contribution of Alternative Transcript Isoforms in Mature Biofilm Growth Phase of <i>Candida glabrata</i>.

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